Kinase control prevents HIV-1 reactivation in spite of high levels of induced NF-κB activity.

Journal of Virology
Frank WolschendorfOlaf Kutsch

Abstract

Despite its clinical importance, the molecular biology of HIV-1 latency control is at best partially understood, and the literature remains conflicting. The most recent description that latent HIV-1 is integrated into actively expressed host genes has further confounded the situation. This lack of molecular understanding complicates our efforts to identify therapeutic compounds or strategies that could reactivate latent HIV-1 infection in patients, a prerequisite for the eradication of HIV-1 infection. Currently, many therapeutic development efforts operate under the assumption that a restrictive histone code could govern latent infection and that either dissipation of the histone-based restrictions or NF-κB activation could be sufficient to trigger HIV-1 reactivation. We here present data that suggest an additional, higher level of molecular control. During a high-content drug screening effort, we identified AS601245 as a potent inhibitor of HIV-1 reactivation in latently infected primary T cells and T cell lines. In either system, AS601245 inhibited HIV-1 reactivation despite high levels of induced NF-κB activation. This finding suggests the presence of a gatekeeper kinase activity that controls latent HIV-1 infection even in...Continue Reading

References

Sep 3, 1992·The New England Journal of Medicine·D AbramowiczM Goldman
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·T M FolksA S Fauci
Oct 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S E Tong-StarksenB M Peterlin
Jul 14, 1995·The Journal of Biological Chemistry·M Karin
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·P GhoshH A Young
Apr 16, 1998·Genes & Development·J PengD H Price
Jul 7, 1998·The Journal of Experimental Medicine·T W ChunA S Fauci
Nov 24, 1999·The Journal of Biological Chemistry·A CivilC L Verweij
Nov 9, 2000·The Journal of Infectious Diseases·J N BlanksonR F Siliciano
Aug 7, 2002·Journal of Virology·Theodore C PiersonRobert F Siliciano
Nov 22, 2002·DNA and Cell Biology·Guocheng HeDavid M Margolis
Sep 23, 2003·Immunity·David G BrooksJerome A Zack
Dec 12, 2003·Nature Reviews. Cancer·Robert Eferl, Erwin F Wagner
Jul 28, 2004·Journal of Molecular Biology·Murali PalangatRobert Landick
Jul 31, 2004·The Journal of Biological Chemistry·Samuel A WilliamsWarner C Greene
Nov 27, 2004·Journal of Cell Science·Jochen HessMarina Schorpp-Kistner
Feb 3, 2005·Nature Reviews. Drug Discovery·Curtis T KeithBrent R Stockwell

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Citations

Apr 2, 2013·Lancet·Christine KatlamaRafick P Sekaly
Jun 28, 2013·Retrovirology·Carine Van LintAlessandro Marcello
Jan 24, 2014·Mediators of Inflammation·Amit KumarGeorges Herbein
Jun 29, 2012·Cytokine & Growth Factor Reviews·Chao Wang, Tania H Watts
Jul 7, 2012·Cytokine & Growth Factor Reviews·Anna Lisa RemoliMarco Sgarbanti
Apr 8, 2017·Cell Cycle·Dorota Piekna-PrzybylskaRobert A Bambara
Dec 22, 2017·Cancers·Jonas CicenasSigitas Urbonavicius
Sep 8, 2015·Oncotarget·Lillian Seu, Olaf Kutsch

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